A novel application, utilizing polyacrylamide-g-carboxymethyl cellulose (CMC-g-PAM) in concentrating dilute solutions of Bovine serum albumin (BSA), was investigated. The grafting reaction parameters were investigated and the hydrogel smartness was verified. FT-IR proved that the grafting reaction occurred between the hydroxyl group located in anhydroglucose C2 position of CMC and the π-bond of PAM and SEM confirmed a changed morphology to a fibrillar structure. The pH sensitivity was proved; as the grafted polymer attained its maximum swelling at pH 7.2 while the minimum swelling was observed under acidic conditions (pH 1-3). The rate of water uptake in the grafted polymer hydrogel was higher than that of the homopolymer hydrogel and the swelling behaviors of both hydrogels obeyed second-order kinetics. The tested hydrogel showed a high potency towards concentrating BSA solutions with a concentration factor of 1 to 4.5 times and recovery of 60–90%. The concentration factor increased linearly with increasing both the polymer concentration and the process time and decreased with the increase in the protein concentration. The grafted polymer had stable efficiency in the concentration process for 20 cycles. The obtained results have recommended the employment of the prepared CMC-g-PAM hydrogel in the down stream protein concentration process in the industrial scale. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011.